SGLT2 inhibitor lowers serum uric acid through alteration of uric acid transport activity in renal tubule by increased glycosuria

Sodium glucose cotransporter 2 (SGLT2) inhibitors have been reported to lower the serum uric acid (SUA) level. To elucidate the mechanism responsible for this reduction, SUA and the urinary excretion rate of uric acid (UE_UA) were analysed after the oral administration of luseogliflozin, a SGLT2 inhibitor, to healthy subjects. After dosing, SUA decreased, and a negative correlation was observed between the SUA level and the UE_UA, suggesting that SUA decreased as a result of the increase in the UE_UA. The increase in UE_UA was correlated with an increase in urinary d ‐glucose excretion, but not with the plasma luseogliflozin concentration. Additionally, in vitro transport experiments showed that luseogliflozin had no direct effect on the transporters involved in renal UA reabsorption. To explain that the increase in UE_UA is likely due to glycosuria, the study focused on the facilitative glucose transporter 9 isoform 2 (GLUT9ΔN, SLC2A9b), which is expressed at the apical membrane of the kidney tubular cells and transports both UA and d ‐glucose. It was observed that the efflux of [¹⁴C]UA in Xenopus oocytes expressing the GLUT9 isoform 2 was trans‐stimulated by 10 mm d ‐glucose, a high concentration of glucose that existed under SGLT2 inhibition. On the other hand, the uptake of [¹⁴C]UA by oocytes was cis‐inhibited by 100 mm d ‐glucose, a concentration assumed to exist in collecting ducts. In conclusion, it was demonstrated that the UE_UA could potentially be increased by luseogliflozin‐induced glycosuria, with alterations of UA transport activity because of urinary glucose. © 2014 The Authors. Biopharmaceutics & Drug Disposition. Published by John Wiley & Sons Ltd.     

Plasma level of asymmetric dimethylarginine (ADMA) as a predictor of carotid intima-media thickness progression: six-year prospective study using carotid ultrasonography

This study was designed to determine the relationship between plasma asymmetric dimethylarginine (ADMA) and the development of carotid atherosclerosis. Cross-sectional studies have revealed that plasma ADMA concentration is correlated with the intima-media thickness (IMT) of the carotid artery, but no prospective studies have appeared. Therefore we prospectively investigated whether or not plasma ADMA level can predict IMT progression. In a community-based cohort, we enrolled 712 subjects who were over 40 years old and who had no apparent cardiovascular diseases according to high-resolution carotid ultrasonography. Blood chemistries including ADMA were measured at baseline. In 575 subjects, IMT was re-measured 6 years later. The value of baseline ADMA for predicting IMT changes was investigated by multivariable analysis. At baseline, there was a significant (beta=0.321; p<0.001) relationship between IMT and ADMA levels. Multiple linear regression analysis revealed that baseline ADMA (beta=0.241; p<0.01) was the only predictor of IMT progression after adjustments for age, sex, baseline IMT, and four major risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) plus hyperuricacidemia. Plasma ADMA was a predictor of carotid IMT progression.     

Usefulness of measuring electrically evoked auditory brainstem responses in children with inner ear malformations during cochlear implantation

Conclusions: EABR is a reliable and effective way of objectively confirming device function and implant-responsiveness of the peripheral auditory neurons up to the level of the brainstem in cases of inner ear malformation. Objective: To investigate the usefulness of measuring the intra-operative electrically evoked compound action potential (ECAP) and electrically evoked auditory brainstem response (EABR) in patients with and without congenital inner ear anomalies during cochlear implantation. Method: Thirty-eight consecutive children (40 ears) aged 5 or younger with congenital profound hearing loss. Twenty-four (25 ears) lacked congenital inner ear anomalies. The 14 patients (15 ears) with a malformation had common cavities (four ears), incomplete partition type I (three ears), cochlea hypoplasia type III (three ears), enlarged vestibular aqueduct (four ears), and cochlear nerve canal stenosis (one ear). Main outcome measures are ECAP and EABR responses. Results: Of the 25 ears lacking any malformation, 21, three, and one showed ‘Good’, ‘Variable’, and ‘No’ ECAP responses, respectively, and 24 and one showed ‘Good’ and ‘Variable’ intra-cochlear responses, respectively. Of the 15 ears with a malformation, two showed ‘Good’ ECAP responses, nine had ‘Variable’ ECAP responses, and four showed ‘No’ ECAP responses. Moreover, five showed ‘Good’ EABR responses and 10 showed ‘Variable’ EABR responses.     

Surgical specialty and outcomes for carotid endarterectomy: evidence from the National Surgical Quality Improvement Program

Background

Carotid endarterectomy (CEA) has been performed since the 1950s and remains one of the most common surgical procedures in the United States. The procedure is performed by cardiothoracic, general, neurologic, and vascular surgeons. This study uses data from the National Surgical Quality Improvement Program (NSQIP) to examine the outcomes after CEA when performed by general or vascular surgeons.

Materials and methods

Data included 34,493 CEAs from years 2005 to 2010 recorded in the NSQIP database. Primary outcomes measured were length of stay, 30-d mortality, surgical site infection, cerebrovascular accident, myocardial infarction, and blood transfusion requirement. Secondary outcomes measured were the remaining intraoperative outcomes from the NSQIP database.

Results

After controlling for patient and surgical characteristics, patients treated by general surgeons did not have a significantly different LOS or 30-d mortality than those treated by vascular surgeons. Patients of general surgeons had nearly twice the risk of acquiring a surgical site infection (odds ratio [OR] = 1.94; P = 0.012), >1.5 times the risk of cerebrovascular accident (OR = 1.56; P = 0.008), and >1.8 times the risk of blood transfusion (OR = 1.85; P = 0.017) than those of vascular surgeons. Patients of general surgeons had less than half the risk of having a myocardial infarction (OR = 0.34; P = 0.031) than those of vascular surgeons.

Conclusions

Surgical specialty is associated with a wide range of postoperative outcomes after CEA. Additional research is needed to explore practice and cultural differences across surgical specialty that may lead to outcome differences.     

A Rare Case of Anterior Chest Wall Schwannoma Masquerading as a Breast Tumor

A schwannoma is a tumor that develops on peripheral nerves or spinal roots. Although any part of the body can be affected, the breast is a quite unusual site for schwannomas. We report herein a case of schwannoma presenting as a breast tumor. In the current case, the tumor showed both clinically and mammographically as a well-defined breast mass. Of interest, sonographically, the well-defined mass appeared to be located in subcutaneous tissue, not in breast parenchyma, and this finding was confirmed histopathologically. These findings indicate the possibility that a schwannoma arising from subcutaneous breast tissue can show exophytic growth to the breast and appear as a breast tumor. In other words, our case implies the possible presence of a “pseudo” breast schwannoma.Key words: Schwannoma, Breast, Breast cancerA schwannoma is a relatively rare neoplasm that occurs from Schwann cells of the peripheral nerve sheath.^1–3 Although schwannomas may occur in any organ, a breast schwannoma is extremely rare and accounts only 2.6% of schwannomas.^1–4 We report herein a case of schwannoma suspected to be a breast tumor. The concern with breast schwannoma is a differential diagnosis, since on mammogram it sometimes resembles a breast cancer or tumor.